Background/Purpose:

Preliminary studies have shown the efficacy of Canakinumab (Ilaris) in patients with Cryopyrin associated periodic syndromes (CAPS). So far, few information is available about the optimal dosage and frequency of administration of Canakinumab, especially in children presenting a more severe phenotype. Aim of the study was to analyse the efficacy and optimal dose regimen of Canakinumab in CAPS patients in 12 months of routinely clinical practice.

Methods:

12 patients (F:M = 7:5, 9 children and 3 adults) with a clinical diagnosis of CINCA (6 patients), Muckle-Wells (MWS) overlapping with CINCA syndrome (3 patients) and MWS (3 patients) were analyzed. Nine out of them carried mutations of NLRP3 gene. All patients were previously enrolled in the CACZ885D2306 trial and followed in an open fashion for 12 months after the end of the study. Modifications of dose and/or frequency were performed according to the judgment of the physician in charge. Complete remission was considered as the absence of clinical manifestations and normal acute phase reactants. Patients with no clinical remission and elevation of acute phase reactants were considered in partial remission. Patients with clinical manifestations and elevation of acute phase reactants were considered in relapse or active.

Results:

At the end of CACZ885D2306 trial (baseline) 7 patients (3 CINCA patients, 1 MWS/CINCA and 3 MWS) were treated with the initial dosage of 2 mg/kg (or 150 mg if weight was higher than 40 Kg) every 8 weeks. Five were in complete remission, 2 CINCA in partial remission. In 5 patients (3 CINCA patients and 2 MWS/CINCA) the dosage was increased to 4 mg/kg (or 300 mg) every 8 weeks. All of them were in partial remission. During observational study, modifications of dosage or frequency were performed in 7/12 patients. The 5 patients who required a higher dosage during the CACZ885D2306 displayed a persistent elevation of acute phase reactants associated, in 2 patients, with a mild clinical disease activity (mild rash, headache, arthralgia). In these patients the frequency of the administration of Canakinumab was gradually increased to 7 weeks (1 CINCA, 1 MWS/CINCA), to 6 weeks in 2 CINCA patients and every 4 weeks in 1 MWS/CINCA patient. At the end of the 12 months of observation 1 patient was in complete remission and 3 in partial remission. In one CINCA patient the treatment was discontinued due to persistence of disease activity and poor compliance. During the 12 month of follow-up other two patients (1 CINCA, 1 MWS) displayed a mild relapse of their diseases that required to increase the frequency of administration (6 and 7 weeks, respectively) without a modification of the dosage (2 mg/kg). In 5 patients (2 MWS, 1 MWS/CINCA and 2 CINCA patients) the treatment was not modified being effective in the control of the disease.

Conclusion:

This study confirms the efficacy of Canakinumab in the control of disease activity in CAPS. However, paediatric patients and those with a more severe phenotype require higher and more frequent dosage than previously described